Kalwitz Gregor, Endres Michaela, Neumann Katja, Skriner Karl, Ringe Jochen, Sezer Orhan, Sittinger Michael, Häupl Thomas, Kaps Christian
TransTissue Technologies GmbH, Tucholskystrasse 2, 10117 Berlin, Germany.
Int J Biochem Cell Biol. 2009 Mar;41(3):649-58. doi: 10.1016/j.biocel.2008.07.011. Epub 2008 Jul 30.
A variety of chemokines has been shown to recruit human bone marrow-derived mesenchymal stem cells (MSC) and may be potential candidates for chemokine-based tissue regeneration approaches. The aim of our study was to determine whether the chemokine CXCL7 stimulates migration of human bone marrow-derived MSC and to analyze the effect of CXCL7 on the recruitment of MSC on the broad molecular level. Chemotaxis assays documented that high doses of CXCL7 significantly recruited MSC. Gene expression profiling using oligonucleotide microarrays showed that MSC treated with CXCL7 differentially expressed genes related to cell migration, cell adhesion and extracellular matrix remodeling. Pathway analysis showed that CXCL7 induced the expression of all chemokines binding the interleukin (IL) receptors A and B, CXCR1 and CXCR2, as well as the IL6 signal transducer (gp130) and its ligands IL6 and leukemia inhibitory factor (LIF). Induction of differentially expressed chemokines CXCL1-3, CXCL5, and CXCL6 as well as LIF and gp130 in MSC by CXCL7 was verified by real-time polymerase chain reaction. Immunoassay of cell culture supernatants confirmed elevated levels of the interleukins 6 and 8 in MSC upon treatment with CXCL7. Chemotaxis assays showed that interleukin 6 did not recruit MSC. In conclusion, CXCL7 significantly stimulates the migration of human MSC in vitro. Pathway analysis suggests that recruitment of human MSC by CXCL7 is supported by the induction of ligands of the interleukin 8 receptors, synergistically activating the respective signaling pathways.
多种趋化因子已被证明可招募人骨髓间充质干细胞（MSC），可能是基于趋化因子的组织再生方法的潜在候选物。我们研究的目的是确定趋化因子CXCL7是否刺激人骨髓来源的MSC迁移，并在广泛的分子水平上分析CXCL7对MSC募集的影响。趋化性分析表明，高剂量的CXCL7可显著募集MSC。使用寡核苷酸微阵列进行的基因表达谱分析表明，用CXCL7处理的MSC差异表达与细胞迁移、细胞粘附和细胞外基质重塑相关的基因。通路分析表明，CXCL7诱导了所有与白细胞介素（IL）受体A和B、CXCR1和CXCR2结合的趋化因子的表达，以及IL6信号转导子（gp130）及其配体IL6和白血病抑制因子（LIF）的表达。通过实时聚合酶链反应验证了CXCL7对MSC中差异表达的趋化因子CXCL1-3、CXCL5和CXCL6以及LIF和gp130的诱导作用。细胞培养上清液的免疫测定证实，用CXCL7处理后，MSC中白细胞介素6和8的水平升高。趋化性分析表明，白细胞介素6不募集MSC。总之，CXCL7在体外显著刺激人MSC的迁移。通路分析表明，CXCL7对人MSC的募集受到白细胞介素8受体配体诱导的支持，协同激活各自的信号通路。
